Cytosine methylation regulates oviposition in the pathogenic blood fluke Schistosoma mansoni

TY - JOUR

T1 - Cytosine methylation regulates oviposition in the pathogenic blood fluke Schistosoma mansoni

AU - Geyer, Kathrin Karola

AU - Rodríguez-López, Carlos Marcelino

AU - Hoffmann, Karl Francis

AU - Chalmers, Iain Wyllie

AU - Munshi, Sabrina Eram

AU - Truscott, Martha

AU - Heald, James Kevin

AU - Wilkinson, Michael J.

AU - Hoffmann, Karl Francis

N1 - Geyer, K. K., Rodriguez Lopez, C. M., Chalmers, I. W., Munshi, S. E., Truscott, M., Heald, J., Wilkinson, M. J., Hoffmann, K. F. (2011). Cytosine methylation regulates oviposition in the pathogenic blood fluke Schistosoma mansoni. Nature Communications, 2, Article No: 424. K.F.H. and M.J.W. conceived the project; J.H. analysed schistosome m5C by GC–MS; C.M.R.L. assisted in the MSAP analysis of schistosome gDNA and provided valuable direction in the practical studies of schistosome DNA methylation; I.W.C. and M.T. assisted in sodium bisulfite conversions, S.E.M. performed the decitabine/adult worm co-cultivations and K.K.G. conducted all remaining experiments reported herein. K.F.H., M.J.W., C.M.R.L. and K.K.G. drafted and edited the manuscript. K.F.H. directed the project and assembled the manuscript. IMPF: 07.39 RONO: 00

PY - 2011/8/9

Y1 - 2011/8/9

N2 - Similar to other metazoan pathogens, Schistosoma mansoni undergoes transcriptional and developmental regulation during its complex lifecycle and host interactions. DNA methylation as a mechanism to control these processes has, to date, been discounted in this parasite. Here we show the first evidence for cytosine methylation in the S. mansoni genome. Transcriptional coregulation of novel DNA methyltransferase (SmDnmt2) and methyl-CpG-binding domain proteins mirrors the detection of cytosine methylation abundance and implicates the presence of a functional DNA methylation machinery. Genome losses in cytosine methylation upon SmDnmt2 silencing and the identification of a hypermethylated, repetitive intron within a predicted forkhead gene confirm this assertion. Importantly, disruption of egg production and egg maturation by 5-azacytidine establishes an essential role for 5-methylcytosine in this parasite. These findings provide the first functional confirmation for this epigenetic modification in any worm species and link the cytosine methylation machinery to platyhelminth oviposition processes.

AB - Similar to other metazoan pathogens, Schistosoma mansoni undergoes transcriptional and developmental regulation during its complex lifecycle and host interactions. DNA methylation as a mechanism to control these processes has, to date, been discounted in this parasite. Here we show the first evidence for cytosine methylation in the S. mansoni genome. Transcriptional coregulation of novel DNA methyltransferase (SmDnmt2) and methyl-CpG-binding domain proteins mirrors the detection of cytosine methylation abundance and implicates the presence of a functional DNA methylation machinery. Genome losses in cytosine methylation upon SmDnmt2 silencing and the identification of a hypermethylated, repetitive intron within a predicted forkhead gene confirm this assertion. Importantly, disruption of egg production and egg maturation by 5-azacytidine establishes an essential role for 5-methylcytosine in this parasite. These findings provide the first functional confirmation for this epigenetic modification in any worm species and link the cytosine methylation machinery to platyhelminth oviposition processes.

U2 - 10.1038/ncomms1433

DO - 10.1038/ncomms1433

M3 - Article

C2 - 21829186

VL - 2

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

M1 - 424

ER -